Scientists study links between obesity, age and body chemistry

Journal of Lipids (2022). DOI: 10.1155/2022/7122738″ width=”800″ height=”530″/>

Comparison of total body weight, liver and WAT between all treatment groups. Total body weight, liver weight, liver somatic index (HSI), WAT weight and WAT somatic index (WSI) were measured for all treatment groups. The data is presented as . Statistical significance was determined by a one-way ANOVA multiple comparison test with Tukey’s multiple comparison test as a post hoc test (). “a” (age) indicates the age difference between young (4.5 months) and old (9 months) mice within the same genotype and diet group, “c” (capture) indicates the difference between young (4.5 months) fed with HFD and ND- mice fed with old mice (9 months) of the same genotype, “d” (diet) indicates the difference in diet between mice fed with ND and fed with HFD in the same genotype and age, and “g” (genotype) indicates the genotype difference between WT and Cyp2b-null mice in the same diet and age group. No asterisk indicates a Journal of Lipids (2022) value. DOI: 10.1155/2022/7122738

A team of scientists from Clemson University is making breakthroughs in understanding the relationship between certain enzymes that are normally produced in the body and their role in regulating obesity and controlling liver disease.

According to data from the Centers for Disease Control and Prevention (CDC) collected in 2017-2018, more than 42% of American adults and 19% of young Americans are obese.

Three Clemson researchers and colleagues from Emory University School of Medicine studied male mice who lacked the Cyp2b enzyme and how the lack of the enzyme affected the mice’s metabolism.

William Baldwin, professor and graduate program coordinator in Clemson’s Department of Biological Sciences, said the research was sparked in part by a simple observation: Male mice lacking the Cyp2b enzyme were gaining weight. The same effect was not noticed in female Cyp2b-null mice.

“We noticed that our Cyp2b-null mice were heavier,” said Baldwin, a professor in the department of biological sciences. “They are more prone to obesity, at least diet-induced obesity, especially in males than wild-type mice, and we were trying to find out why.”

While the observation that informed the researchers was quite simple, it turned out that understanding the interactions behind weight gain would be much more complex.

“It would be nice if there was a simple and pleasant answer,” Baldwin said, “but there probably isn’t a simple and pleasant answer.”

Variety of roles

Baldwin noted the complexity of many chemical processes involving the CYP enzyme, which is part of a superfamily of enzymes that plays various roles in humans. He said Cyp2b enzymes help metabolize certain toxins and drugs to remove them from the body.

But these same CYP enzymes also have other functions. “They metabolize bile acids; they metabolize steroid hormones; they metabolize polyunsaturated fats of our food,” Baldwin said. “That means all of these things can also interact. If you have a high fat diet, this could inhibit the metabolism of your medications. Of course… drugs can inhibit your fat metabolism, affect your steroid metabolism, etc.

The researchers also looked at the association between “disturbed lipid profiles” and disease.

Disease susceptibility and overall health are greatly affected by changes in the lipidome, the researchers noted. High-fat diets, such as the Western diet, cause obesity and drastically alter the liver lipidome, and disrupted lipid profiles are associated with liver diseasesuch as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).






Credit: Clemson University

Impact of age and diet

Baldwin directed Previous search in the relationship between food and environmental toxicants. The most recent study focused on the impact of age and diet on these metabolic processes.

“What does a bad diet do to us? What does age do to us? That’s kind of the idea here,” Baldwin said of the latest research. “We are looking at these enzymes; what might happen over time to our profiles in this mouse model compared to a single wild-type mouse. What might happen over time on a high fat diet, what might happen with age, and how does it differ between this mouse model, which does not have these enzymes, compared to the one who has these enzymes? »

Simply put, Baldwin said: “One of the things we’ve seen, and it’s not surprising, is that getting older is bad. It’s harder for mice to regulate their body weight. They take weight The weight they have is more white adipose tissue [connective tissue mainly comprising fat cells]. …and some of those things were a little worse in mice that lacked the Cyp2b enzymes. They were a bit heavier. They had a bit more fat than their counterparts. Their livers were a little bigger and a little less healthy. So they had a lot of those things that we associate with age.”

The diet also had an impact on the health of the mice.

“Of course, the diet didn’t help either,” Baldwin continued. “It’s the same case: eating a a poor diet made you gain weight, and it was a little worse with these [Cyp2b-null] mouse, probably due to poor metabolism.”

He said the exact mechanism by which the Cyp2b enzyme works is not fully understood.

“You take away an enzyme that helps metabolize them, but I don’t think it’s really important that it helps get rid of the fat, but that it lets the body know the fat is there. It produces probably signaling molecules that say, ‘Hey, we have to decide what we’re going to do with this fat; we have to distribute this fat.’ That kind of information. It’s just an educated guess at the moment, but I think that’s probably what’s happening.”

Differences in humans

Baldwin said his current research takes a closer look at the mechanisms that are at play and how they differ in a human model from mouse studies. He said the research, which will be part of an unpublished paper, indicates that mouse and human enzymes probably don’t work in exactly the same way. “The human enzyme seems to make us keep some of the fat in the liver, and the mouse enzyme seems to lead this to white adipose tissue. There are clues here in this article that this is the case,” Baldwin said.

The results of the study were published in the Lipid Diary in a paper titled “Age- and diet-dependent changes in hepatic lipid profiles of phospholipids in male mice: age acceleration in Cyp2b-Null mice”.


Researchers link metabolic enzyme to obesity and fatty liver disease


More information:
Melissa M. Heintz et al, Age and diet-dependent changes in hepatic lipid profiles of phospholipids in male mice: age acceleration in Cyp2b-Null mice, Lipid Diary (2022). DOI: 10.1155/2022/7122738

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